DESCRIPTION: (Applicant's Abstract) Candidate: John Casada, M.D., Ph.D. is an Assistant Professor engaged in research and clinical care focusing on posttraumatic stress disorder (PTSD). His primary career goal is to become an independent investigator conducting clinical research on the interaction of PTSD and sedative drug abuse. Though he has completed training in basic neuroscience and has conducted psychophysiology research in PTSD, he has no training in substance abuse research. Therefore, he plans to pursue training in grant preparation, human laboratory research methods, data interpretation, manuscript preparation, and operant behavioral theories essential to substance abuse research. Environment: Dr. Casada has received departmental support for his PTSD studies and the support of his chairman, Charles Bowden, M.D., in establishing the Emotional Trauma Program, which serves to coordinate PTSD research activities at the University Hospital System and Veterans Administration Hospital. This Mentored Career Development Award will allow Dr. Casada to formalize a mentoring relationship with John Roache, Ph.D. and provide protected time to develop research expertise and career development opportunities in collaboration with the NIDA-funded researchers in the Division of Alcohol and Drug Addiction Research. The proposed research will use human laboratory techniques to assess the role of highly arousing, negative valence emotional states, such as anxiety and anger, to promote self-medication with benzodiazepines and alcohol in PTSD patients. To accomplish this, four tasks (Guided Muscle Relaxation, Stroop Color-Word Task, Script-Driven Imagery, and the Point Subtraction Aggression Paradigm) will be used to experimentally vary levels of arousal and negative valence in 18 PTSD patients and 18 subjects who have experienced trauma but never developed PTSD. Motivation and preference for alprazolam and alcohol will be assessed by the Multiple Choice Questionnaire (MCQ) under double blind, double dummy conditions. Emotional responses will be assessed using skin conductance and heart rate as measures of arousal, corrugator electromyogram as an indicator of negative valence, and anxiety and anger ratings as self-report measures of subjective mood. This experiment will be the first to assess sedative drug self-administration in PTSD patients under controlled conditions in the human laboratory. These data will determine the role of anxiety and anger types of emotional reactions as a motive for self-medication in PTSD patients. More importantly, the data also will provide practical information for the clinical treatment of PTSD patients and others with anxiety who may be at risk for abusing prescription anxiolytics or alcohol.